Hidden Appendicoliths and Their Impact on the Severity and Treatment of Acute Appendicitis.

Background/Objectives: In patients diagnosed with uncomplicated acute appendicitis (UAA), the absence of calcified deposits or stones, called appendicoliths, often leads to consideration of non-operative treatment (NOT), despite the notable treatment failure rate associated with this approach. Previous research has indirectly estimated the prevalence of appendicoliths to range between 15% and 38% retrospectively by CT scan, intraoperative palpation, and pathology report, thereby potentially missing certain concrements. Our hypothesis proposes that this reported prevalence significantly underestimates the occurrence of appendicoliths, which could explain the high failure rate of 29% of patients with appendicitis observed with NOT. Methods: In our prospective study, conducted with a cohort of 56 adult patients diagnosed with acute appendicitis (AA), we employed intraoperative extracorporeal incisions of the vermiform appendix, in addition to standard diagnostic methods. Results: Our findings revealed 50% more appendicoliths by intraoperative incision (n = 36, p < 0.001) compared to preoperative imaging (n = 24). Appendicoliths were present in 71.4% (n = 40, p < 0.001) of AA patients. Conclusions: These results suggest that conventional diagnostic procedures plausibly underestimate the actual prevalence of appendicoliths, potentially elucidating the frequent treatment failures observed in NOT approaches applied to patients with UAA.

Surgical Outcome and Microbial Colonization of Standardized Smear Locations after Pancreatic Head Resection (Pylorus-Preserving Pancreatoduodenectomy, PPPD) for Chronic Pancreatitis and Pancreatic Head Carcinoma.

Introduction: Patients with chronic pancreatitis (CP) as well as with pancreatic head carcinoma (CA) undergo the surgical intervention named "pylorus-preserving pancreatoduodenectomy according to Traverso-Longmire (PPPD)", which allowed a comparative analysis of the postoperative courses. The hypothesis was that patients with CA would have worse general as well as immune status than patients with CP due to the severity of the tumor disease and that this would be reflected in the more disadvantageous early postoperative outcome after PPPD. Methods: With the aim of eliciting the influence of the different diagnoses, the surgical outcome of all consecutive patients who underwent surgery at the Dept. of General, Abdominal, Vascular and Transplant Surgery at the University Hospital at Magdeburg between 2002 and 2015 (inclusion criterion) was recorded and comparatively evaluated. Early postoperative outcome was characterized by general and specific complication rate indicating morbidity, mortality, and microbial colonization rate, in particular surgical site infection (SSI, according to CDC criteria). In addition, microbiological findings of swabs and cultures from all compartments as well as preoperative and perioperative parameters from patient records were retrospectively documented and used for statistical comparison in this systematic retrospective unicenter observational study (design). Results: In total, 192 cases with CA (68.1%) and 90 cases with CP (31.9%) met the inclusion criteria of this study. Surprisingly, there were similar specific complication rates of 45.3% (CA) vs. 45.6% (CP; p = 0.97) and in-hospital mortality, which differed only slightly at 3.65% (CA) vs. 3.3% (CP; p = 0.591); the overall complication rate tended to be higher for CA at 23.4% vs. 14.4% (CP; p = 0.082). Overall, potentially pathogenic germs were detected in 28.9% of all patients in CP compared to 32.8% in CA (p = 0.509), and the rate of SSI was 29.7% (CA) and 24.4% (CP; p = 0.361). In multivariate analysis, CA was found to be a significant risk factor for the development of SSI (OR: 2.025; p = 0.048); the underlying disease had otherwise no significant effect on early postoperative outcome. Significant risk factors in the multivariate analysis were also male sex for SSI and microbial colonization, and intraoperatively transfused red cell packs for mortality, general and specific complications, and surgical revisions. Conclusions: Based on these results, a partly significant, partly trending negative influence of the underlying disease CA, compared to CP, on the early postoperative outcome was found, especially with regard to SSI after PPPD. This influence is corroborated by the international literature.

Unlocking Clinical Insights: Lymphocyte-Specific Protein Tyrosine Kinase Candidates as Promising Therapeutic Targets for Pancreatic Cancer Risk Stratification.

Background: Uncover the pivotal link between lymphocyte-specific protein tyrosine kinase (Lck)-related genes and clinical risk stratification in pancreatic cancer. Methods: This study identifies shared genes between differentially expressed genes (DEGs) and Lck-related genes in pancreatic cancer using a methodological framework rooted in The Cancer Genome Atlas database. Feature gene selection is accomplished and a signature model is constructed. Statistical significant clinical endpoints such as overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) were defined. Results: After performing random survival forest, Lasso regression, and multivariate Cox regression model, 7 trait genes out of 272 Lck-associated DEGs are selected to create a signature model that is independent of other clinical factors and can predict OS and DSS. It appears that high-risk patients have activated the TP53 signaling pathway and the cell cycle signaling pathway. LAMA3 turned out to be the hub gene of the signature with high expression in pancreatic cancer. Patients with increased expression of LAMA3 had a short OS, DSS, and PFI in comparison. The candidate competing endogenous RNA network of LAMA3 turned out to be OPI5-AS1/hsa-miR-186-5p/LAMA3 axis. Conclusions: A characteristic signature of seven Lck-related genes, especially LAMA3, has been shown to be a key factor in clinical risk stratification for pancreatic cancer.

Influence of Certification Program on Treatment Quality and Survival for Rectal Cancer Patients in Germany: Results of 13 Certified Centers in Collaboration with AN Institute.

INTRODUCTION: The certification of oncological units as colorectal cancer centers (CrCCs) has been proposed to standardize oncological treatment and improve the outcomes for patients with colorectal cancer (CRC). The proportion of patients with CRC in Germany that are treated by a certified center is around 53%. Lately, the effect of certification on the treatment outcomes has been critically discussed. AIM: Our aim was to investigate the treatment outcomes in patients with rectal carcinoma at certified CrCCs, in German hospitals of different medical care levels. METHODS: We performed a retrospective analysis of a prospective, multicentric database (AN Institute) of adult patients who underwent surgery for rectal carcinoma between 2002 and 2016. We included 563 patients from 13 hospitals of different medical care levels (basic, priority, and maximal care) over periods of 5 years before and after certification. RESULTS: The certified CrCCs showed a significant increase in the use of laparoscopic approach for rectal cancer surgery (5% vs. 55%, p < 0.001). However, we observed a significantly prolonged mean duration of surgery in certified CrCCs (161 Min. vs. 192 Min., p < 0.001). The overall morbidity did not improve (32% vs. 38%, p = 0.174), but the appearance of postoperative stool fistulas decreased significantly in certified CrCCs (2% vs. 0%, p = 0.036). Concerning the overall in-hospital mortality, we registered a positive trend in certified centers during the five-year period after the certification (5% vs. 3%, p = 0.190). The length of preoperative hospitalization (preop. LOS) was shortened significantly (4.71 vs. 4.13 days, p < 0.001), while the overall length of in-hospital stays was also shorter in certified CrCCs (20.32 vs. 19.54 days, p = 0.065). We registered a clear advantage in detailed, high-quality histopathological examinations regarding the N, L, V, and M.E.R.C.U.R.Y. statuses. In the performed subgroup analysis, a significantly longer overall survival after certification was registered for maximal medical care units (p = 0.029) and in patients with UICC stage IV disease (p = 0.041). In patients with UICC stage III disease, we registered a slightly non-significant improvement in the disease-free survival (UICC III: p = 0.050). CONCLUSIONS: The results of the present study indicate an improvement in terms of the treatment quality and outcomes in certified CrCCs, which is enforced by certification-specific aspects such as a more differentiated surgical approach, a lower rate of certain postoperative complications, and a multidisciplinary approach. Further prospective clinical trials are necessary to investigate the influence of certification in the treatment of CRC patients.

The Pancreas as a Target of Metastasis from Renal Cell Carcinoma: Is Surgery Feasible and Safe? A Single-Center Experience in a High-Volume and Certified Pancreatic Surgery Center in Germany.

Background: Secondary malignant tumors of the pancreas are rare, representing 2-5% of all pancreatic malignancies. Nevertheless, the pancreas is one of the target organs in cases of metastatic clear cell renal cell carcinoma (CCRCC). Additionally, recurrent metastasis may occur. Surgical resection remains the best and prognostically most favorable therapeutic option in cases of solitary pancreatic metastasis. Aim: To review retrospectively the clinical tumor registry of the University Hospital of Magdeburg, Germany, for this rare entity, performing a clinical systematic single-center observational study (design). Methods: A retrospective cohort analysis of consecutive patients who had undergone pancreatic resection for metastatic CCRC was performed in a single high-volume certified center for pancreatic surgery in Germany from 2010 to 2022. Results: All patients (n = 17) included in this study had a metachronous metastasis from a CCRCC. Surgery was performed at a median time interval of 12 (range, 9-16) years after primary resection for CCRCC. All 17 patients were asymptomatic at the time of diagnosis. Three of those patients (17.6%) presented with recurrent metastasis in a different part of the pancreas during follow-up. In a total of 17 patients, including those with recurrent disease, a surgical resection was performed; Pancreatoduodenectomy was performed in 6 patients (35%); left pancreatectomy with splenectomy was performed in 7 patients (41%). The rest of the patients underwent either a spleen-preserving pancreatic tail resection, local resection of the tumor lesion or a total pancreatectomy. The postoperative mortality rate was 6%. Concerning histopathological findings, seven patients (41%) had multifocal metastasis. An R0 resection could be achieved in all cases. The overall survival at one, three and five years was 85%, 85% and 72%, respectively, during a median follow-up of 43 months. Conclusions: CCRC pancreatic metastases can occur many years after the initial treatment of the primary tumor. Surgery for such a malignancy seems feasible and safe; it offers very good short- and long-term outcomes, as indicated. A repeated pancreatic resection can also be safely performed.

Study International Multicentric Pancreatic Left Resections (SIMPLR): Does Surgical Approach Matter?

BACKGROUND: Minimally invasive surgery is increasingly preferred for left-sided pancreatic resections. The SIMPLR study aims to compare open, laparoscopic, and robotic approaches using propensity score matching analysis. METHODS: This study included 258 patients with tumors of the left side of the pancreas who underwent surgery between 2016 and 2020 at three high-volume centers. The patients were divided into three groups based on their surgical approach and matched in a 1:1 ratio. RESULTS: The open group had significantly higher estimated blood loss (620 mL vs. 320 mL, p < 0.001), longer operative time (273 vs. 216 min, p = 0.003), and longer hospital stays (16.9 vs. 6.81 days, p < 0.001) compared to the laparoscopic group. There was no difference in lymph node yield or resection status. When comparing open and robotic groups, the robotic procedures yielded a higher number of lymph nodes (24.9 vs. 15.2, p = 0.011) without being significantly longer. The laparoscopic group had a shorter operative time (210 vs. 340 min, p < 0.001), shorter ICU stays (0.63 vs. 1.64 days, p < 0.001), and shorter hospital stays (6.61 vs. 11.8 days, p < 0.001) when compared to the robotic group. There was no difference in morbidity or mortality between the three techniques. CONCLUSION: The laparoscopic approach exhibits short-term benefits. The three techniques are equivalent in terms of oncological safety, morbidity, and mortality.

Integrating a microRNA signature as a liquid biopsy-based tool for the early diagnosis and prediction of potential therapeutic targets in pancreatic cancer.

INTRODUCTION: Pancreatic cancer is a highly aggressive cancer, and early diagnosis significantly improves patient prognosis due to the early implementation of curative-intent surgery. Our study aimed to implement machine-learning algorithms to aid in early pancreatic cancer diagnosis based on minimally invasive liquid biopsies. MATERIALS AND METHODS: The analysis data were derived from nine public pancreatic cancer miRNA datasets and two sequencing datasets from 26 pancreatic cancer patients treated in our medical center, featuring small RNAseq data for patient-matched tumor and non-tumor samples and serum. Upon batch-effect removal, systematic analyses for differences between paired tissue and serum samples were performed. The robust rank aggregation (RRA) algorithm was used to reveal feature markers that were co-expressed by both sample types. The repeatability and real-world significance of the enriched markers were then determined by validating their expression in our patients' serum. The top candidate markers were used to assess the accuracy of predicting pancreatic cancer through four machine learning methods. Notably, these markers were also applied for the identification of pancreatic cancer and pancreatitis. Finally, we explored the clinical prognostic value, candidate targets and predict possible regulatory cell biology mechanisms involved. RESULTS: Our multicenter analysis identified hsa-miR-1246, hsa-miR-205-5p, and hsa-miR-191-5p as promising candidate serum biomarkers to identify pancreatic cancer. In the test dataset, the accuracy values of the prediction model applied via four methods were 94.4%, 84.9%, 82.3%, and 83.3%, respectively. In the real-world study, the accuracy values of this miRNA signatures were 82.3%, 83.5%, 79.0%, and 82.2. Moreover, elevated levels of these miRNAs were significant indicators of advanced disease stage and allowed the discrimination of pancreatitis from pancreatic cancer with an accuracy rate of 91.5%. Elevated expression of hsa-miR-205-5p, a previously undescribed blood marker for pancreatic cancer, is associated with negative clinical outcomes in patients. CONCLUSION: A panel of three miRNAs was developed with satisfactory statistical and computational performance in real-world data. Circulating hsa-miRNA 205-5p serum levels serve as a minimally invasive, early detection tool for pancreatic cancer diagnosis and disease staging and might help monitor therapy success.

Management of acute appendicitis during COVID-19 pandemic. Single center data from a tertiary care hospital in Germany.

Objectives: The unexpected global overload of the health system during COVID-19 pandemic has caused changes in management of acute appendicitis worldwide. Whereas conservative treatment was widely recommended, the appendicectomy remained standard therapy in Germany. We aimed to investigate the impact of COVID-19 pandemic on treatment routine for acute appendicitis at University Hospital of Magdeburg. Methods: Adult patients with clinical and/or radiological diagnosis of acute appendicitis were included in the single center retrospective study. Data was collected to patient demographics, treatment modality and outcomes including morbidity and length of stay. The patient data related to COVID-19 period from March 22, 2020 to December 31, 2021 (649 days) were compared to the Non-COVID-19 period from June 12, 2018 to March 21, 2020 (649 days). Subgroup analysis related to conservative or surgical treatment has been performed. Results: A total of 385 patients was included in the study, 203 (52.73 %) during Non-COVID-19 period and 182 (47.27 %) during COVID-19 period. Mean age of entire collective was 43.28 years, containing 43.9 % female patients (p=0.095). Conservative treatment was accomplished in 49 patients (12.7 % of entire collective), increasing from 9.9 % to 15.9 % during COVID-19 period (p=0.074). Laparoscopic appendicectomy was performed in 99.3 % (n=152) of operated patients during COVID-19 period (p=0.013), followed by less postoperative complications compared to reference period (23.5 % vs. 13.1 %, p=0.015). The initiation of antibiotic therapy after the diagnosis increased from 37.9 % to 53.3 % (p=0.002) during COVID-19 period regardless the following treatment modality. Antibiotic treatment showed shorter duration during pandemic period (5.57 days vs. 3.16 days, p<0.001) and it was given longer in the conservative treatment group (5.63 days vs. 4.26 days, p=0.02). The overall length of stay was shorter during COVID-19 period (4.67 days vs. 4.12 days, p=0.052) and in the conservative treatment group (3.08 days vs. 4.47 days, p<0.001). However, the overall morbidity was lower during the COVID-19 period than before (17.2 % vs. 7.7 %, p=0.005) and for conservative therapy compared to appendicectomy (2 % vs. 14.3 %, p=0.016). There was no mortality documented. Conclusions: According to our findings the COVID-19 pandemic had a relevant impact on treatment of acute appendicitis, but it was possible to maintain the traditional diagnostic and treatment pathway. Although laparoscopic appendicectomy remains a recommended procedure, the conservative treatment of uncomplicated appendicitis with excellent short-term outcome can be a safe alternative to surgery during potential new wave of COVID-19 pandemic and in the daily routine.

Does Robotic Liver Surgery Enhance R0 Results in Liver Malignancies during Minimally Invasive Liver Surgery?-A Systematic Review and Meta-Analysis.

BACKGROUND: Robotic procedures are an integral part of modern liver surgery. However, the advantages of a robotic approach in comparison to the conventional laparoscopic approach are the subject of controversial debate. The aim of this systematic review and meta-analysis is to compare robotic and laparoscopic liver resection with particular attention to the resection margin status in malignant cases. METHODS: A systematic literature search was performed using PubMed and Cochrane Library in accordance with the PRISMA guidelines. Only studies comparing robotic and laparoscopic liver resections were considered for this meta-analysis. Furthermore, the rate of the positive resection margin or R0 rate in malignant cases had to be clearly identifiable. We used fixed or random effects models according to heterogeneity. RESULTS: Fourteen studies with a total number of 1530 cases were included in qualitative and quantitative synthesis. Malignancies were identified in 71.1% (n = 1088) of these cases. These included hepatocellular carcinoma, cholangiocarcinoma, colorectal liver metastases and other malignancies of the liver. Positive resection margins were noted in 24 cases (5.3%) in the robotic group and in 54 cases (8.6%) in the laparoscopic group (OR = 0.71; 95% CI (0.42-1.18); p = 0.18). Tumor size was significantly larger in the robotic group (MD = 6.92; 95% CI (2.93-10.91); p = 0.0007). The operation time was significantly longer in the robotic procedure (MD = 28.12; 95% CI (3.66-52.57); p = 0.02). There were no significant differences between the robotic and laparoscopic approaches regarding the intra-operative blood loss, length of hospital stay, overall and severe complications and conversion rate. CONCLUSION: Our meta-analysis showed no significant difference between the robotic and laparoscopic procedures regarding the resection margin status. Tumor size was significantly larger in the robotic group. However, randomized controlled trials with long-term follow-up are needed to demonstrate the benefits of robotics in liver surgery.

[Influence of the COVID-19 pandemic on robotic visceral surgery in Germany]. / Auswirkungen der COVID-19-Pandemie auf die robotische Viszeralchirurgie in Deutschland.

BACKGROUND: Robotic procedures are gaining more and more importance in visceral surgery and seem to develop into an indispensable tool in minimally invasive visceral surgery. In 2020 the COVID-19 pandemic caused unexpected changes in daily surgical routines with still ongoing challenges. We evaluated the impact of the COVID-19 pandemic on robotic visceral procedures and the associated training provided in Germany. MATERIAL AND METHODS: We performed a thorough evaluation of German hospitals and identified 89 surgical departments performing robotic visceral procedures. After extensive topic-related literature search an online questionnaire was developed. It included 35 questions referring to all relevant topics on robotic surgery, such as training programs and influence of the COVID-19 pandemic. The survey was sent via email three times to each department. Descriptive and subgroup analysis were performed. RESULTS: We reported a response to our questionnaire from 22 (24.7%) surgical departments and17 questionnaires were analyzable. The vast majority of them weresurgical departments of university hospitals (58.8%), 17.6% maximum care clinics and 23.5% main care clinics. Robotic procedures were performed for the upper gastrointestinal tract (UGI 88.2%), the hepatopancreaticobiliary system (HPB 82.4%), in the colorectal region (94.1%) and for hernias (35.3%). The relative proportion of robotic operations in comparison to all visceral procedures was between 0.3% and 15.4%. The average conversion rate was 4.6 ± 3.2% referring to 2020. All participating clinics used the robotic DaVinci® system (Intuitive Surgical Inc., CA, USA). In summary 22 robotic systems were used mainly in an interdisciplinary setting (82.4%). For teaching purposes, 7 departments (41.2%) provided a second robotic console. On average 13.2 ± 6.5% of surgeons per clinic were involved in robotic procedures. Defined operating room (OR) teams (82.4%) consisted of consultants, specialists and residents. Team training for surgeons and OR nurses was mainly (52.9%) based on clinic-specific programs. Due to the COVID-19 pandemic the number of robotic procedures decreased in 70.0% of the participating departments compared to 2019 with the highest decline reported during the second quarter of 2020 (64.7%). Referring to this, staff shortage of non-surgical disciplines (anesthesiologists 35.3%, OR nurses 35.3%, intensive care medics 17.6%), COVID-19-specific regulations (58.8%) and limited capacities of intensive and intermediate care (47.1%) were specified as underlying causes. Due to the COVID-19 pandemic, caused by a decline in numbers of robotic procedures, robotic training was paused completely in assistance at the operating table in 23.5% and at the second console in 42.9%. CONCLUSION: Robotic visceral surgery is already implemented with a broad spectrum of operations in many German clinics of different care levels; however, the relative proportion of robotic procedures is low, when compared to the overall caseload of each clinic. Training concepts are heterogeneous and focused on experts. In surgeons with growing experience in robotic surgery, conversion rates are recorded to be very low. There was a negative impact on robotic case numbers and training provided in 2020 caused by the COVID-19 pandemic. Therefore, a further endorsement of robotic training programs and an improvement of training designs seem to be essential tools in order to enforce robotic procedures in visceral surgery.

The LiMAx Test as Selection Criteria in Minimally Invasive Liver Surgery.

BACKGROUND: Liver failure is a crucial predictor for relevant morbidity and mortality after hepatic surgery. Hence, a good patient selection is mandatory. We use the LiMAx test for patient selection for major or minor liver resections in robotic and laparoscopic liver surgery and share our experience here. PATIENTS AND METHODS: We identified patients in the Magdeburg registry of minimally invasive liver surgery (MD-MILS) who underwent robotic or laparoscopic minor or major liver surgery and received a LiMAx test for preoperative evaluation of the liver function. This cohort was divided in two groups: patients with normal (LiMAx normal) and decreased (LiMAx decreased) liver function measured by the LiMAx test. RESULTS: Forty patients were selected from the MD-MILS regarding the selection criteria (LiMAx normal, n = 22 and LiMAx decreased, n = 18). Significantly more major liver resections were performed in the LiMAx normal vs. the LiMAx decreased group (13 vs. 2; p = 0.003). Hence, the mean operation time was significantly longer in the LiMAx normal vs. the LiMAx decreased group (356.6 vs. 228.1 min; p = 0.003) and the intraoperative blood transfusion significantly higher in the LiMAx normal vs. the LiMAx decreased group (8 vs. 1; p = 0.027). There was no significant difference between the LiMAx groups regarding the length of hospital stay, intraoperative blood loss, liver surgery related morbidity or mortality, and resection margin status. CONCLUSION: The LiMAx test is a helpful and reliable tool to precisely determine the liver function capacity. It aids in accurate patient selection for major or minor liver resections in minimally invasive liver surgery, which consequently serves to improve patients' safety. In this way, liver resections can be performed safely, even in patients with reduced liver function, without negatively affecting morbidity, mortality and the resection margin status, which is an important predictive oncological factor.

Laparoscopic cholecystectomy during the COVID-19 pandemic in a tertiary care hospital in Germany: higher rates of acute and gangrenous cholecystitis in elderly patients.

BACKGROUND: The COVID-19 pandemic caused a global health crisis in 2020. This pandemic also had a negative impact on standard procedures in general surgery. Surgeons were challenged to find the best treatment plans for patients with acute cholecystitis. The aim of this study is to investigate the impact of the COVID-19 pandemic on the outcomes of laparoscopic cholecystectomies performed in a tertiary care hospital in Germany. PATIENTS AND METHODS: We examined perioperative outcomes of patients who underwent laparoscopic cholecystectomy during the pandemic from March 22, 2020 (first national lockdown in Germany) to December 31, 2020. We then compared these to perioperative outcomes from the same time frame of the previous year. RESULTS: A total of 182 patients who underwent laparoscopic cholecystectomy during the above-mentioned periods were enrolled. The pandemic group consisted of 100 and the control group of 82 patients. Subgroup analysis of elderly patients (> 65 years old) revealed significantly higher rates of acute [5 (17.9%) vs. 20 (58.8%); p = 0.001] and gangrenous cholecystitis [0 (0.0%) vs. 7 (20.6%); p = 0.013] in the "pandemic subgroup". Furthermore, significantly more early cholecystectomies were performed in this subgroup [5 (17.9%) vs. 20 (58.8%); p = 0.001]. There were no significant differences between the groups both in the overall and subgroup analysis regarding the operation time, intraoperative blood loss, length of hospitalization, morbidity and mortality. CONCLUSION: Elderly patients showed particularly higher rates of acute and gangrenous cholecystitis during the pandemic. Laparoscopic cholecystectomy can be performed safely in the COVID-19 era without negative impact on perioperative results. Therefore, we would assume that laparoscopic cholecystectomy can be recommended for any patient with acute cholecystitis, including the elderly.